1. Field of the Invention
The present invention relates to a novel D-phenyllactic acid dehydrogenase (occasionally abbreviated to “D-PLDH” hereinafter) for producing optically active 2-hydroxy acid derivatives, such as (R)-2-hydroxy-3-phenylpropionic acid (occasionally abbreviated to “D-phenyllactic acid” hereinafter) or derivatives thereof, and to a gene encoding this enzyme.
2. Background Art
D-phenyllactic acid is a precursor of the substance PF1022 [cyclo(D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-methylleucyl-D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-methylleucyl)] which is produced by the filamentous fungus strain PF1022 (Mycelia sterilia, FERM BP-2671) that belongs to Agonomycetales (Sasaki, T. et al., J. Antibiotics, 45, 692 (1992)). Recently, an enzyme which directly produces the substance PF1022 and a gene of this enzyme were revealed (WO01/18179A1). Further, it is known that when a phenyllactic acid derivative is added from outside during the culture of the substance PF1022-producing strain in a liquid medium, a novel substance PF1022 can be produced into which the added phenyllactic acid derivate is incorporated (WO 97/20945). In this case, a precursor to be added is desirably an (R)-2-hydroxy derivative.
Certain kinds of enzymes produced by microorganisms are known to specifically produce optically active compounds, such as D-lactic acid (Taguchi, H. et al., J. Biol. Chem., 266, 12588 (1991)). Further, there have been a number of reports on methods of producing industrially useful compounds such as (R)-2-hydroxy-4-phenylbutyric acid by using certain kinds of enzymes or microorganisms which produce useful enzymes (Japanese Patent No. 2750017, Japanese Patent No. 2752754, Japanese Patent No. 2774341, Japanese Patent No. 2873236, Japanese Patent Publication No. 61271/1994, Japanese Patent Laid-open Publication No. 197774/1994, and Japanese Patent Laid-open Publication No. 75797/1998). Enzymzatic reactions are characterized in producing a target compound more selectively and efficiently than chemical syntheses. On the other hand, it is necessary to search enzymes that specifically act on target compounds because substrate specificity of each enzyme is strict. So far, there has been no report on a dehydrogenase enzyme which is specific to D-phenyllactic acid derived from microorganisms.